To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (ANkx/ANkx) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 ANkx/ANkx mice) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from the original embryonic stem cell line was tested. This second line also develops SCC indistinguishable from the first (15/15 ANkx/ANkx mice). In ANkx/ANkx mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis. To study tumorogenesis in these mice we are comparing the mRNA and protein profiles of the tumor and wild-type tongue epithelial cells during early mouse development.